This laboratory is interested in examining the enzymes which metabolize carcinogens to determine: a) if the enzymes vary in the human population, b) if the variation is genetically determined, and c) if the variation is related to cancer risk. We have confirmed the report of others that aryl hydrocarbon hydroxylase (AHH) does vary in the population and that much of the variation is genetically determined. However we have also shown that the genetic variation is not related to lung cancer risk. We now propose to continue the overall objectives stated above by developing an analytical method for the separation of the multiple P450 microsomal enzymes and by developing assays for other steps in the metabolism of carcinogens, namely epoxide hydrase, glutathione transferase, glucuronyl transferase, and sulfotransferase. We will then examine each of these for genetic variation in humans. We will attempt to determine the molecular basis of the AHH genetic polymorphism and to continue the analysis of the circannual rhythm in AHH activity which we discovered.